(Wrong) lessons learned
The main way we approach an outbreak today is to gather the maximum
amount of data available to suggest pathways of containment. Although
effects of an epidemic are felt throughout all sectors from tourism to
education all the way to the job market, proactive initiatives are
typically assigned to only two key fields: research and public health
(6,7). Consistent
throughout the majority of the reports and studies is the general aim of
increasing preparedness measures
(7,8), which translates
into two major suggested outputs:
Rapid response: the main direction for developments in public
health is improving preparedness. This involves decreasing the time
required to identify and respond to an emerging disease.
Identification of a public health event of international concern
(PHEIC) requires investment into outbreak surveillance, healthcare
data management, reaction protocols and real-time communication
channels between local health authorities and regional or global
organisations (7,9).
Response on the other hand warrants sufficient capacity in healthcare
infrastructure to treat incoming waves of patients, and therefore
relies on stockpiling equipment and medication and increasing the
number of trained healthcare professionals
(6,10).
Focused research: the main directions for developments in
science is increasing our knowledge on the emerging disease. A typical
reaction to an epidemiological emergency is the reallocation of
research funds towards studies targeting the emergent pathogen, which
shifts the focus of novel and existing labs. Unfortunately, analyses
show that this heightened attention and support wanes with the
decreasing sense of emergency and proves to be inefficient in the long
term, thus often referred to as ‘boom-and-bust’ funding
(11,12).
Both outputs have had significant results in managing re-emergence of
known diseases and managing epidemics that are considered regular
occurrences in particular regions, but neither has yielded any
considerable advantages against the EID crisis
(9,13). The reason is
that all of the initiatives listed above require the prior knowledge of
the emergent pathogen. Public health needs to ‘know what they’re looking
for’ to detect it and alert health systems at an early stage of the
outbreak. Otherwise the only clue of a recent emergence is the sudden
spike of patients producing similar symptoms with unknown aetiology, as
was the case for SARS-CoV-2
(14) the 2015 Zika epidemic
(15), or even the currently
ongoing outbreaks of hepatitis among children
(16). Response also requires
data on the clinical manifestations, morbidity and mortality to
adequately prepare healthcare infrastructures, and focusing research
requires an already identified and defined target pathogen or disease.
In case of a newly emerging disease, none of the above described
information is available, crisis response is therefore constantly
lagging behind the spread of the epidemic. Taking into consideration the
effects of globalised travel and trade
(13,17), preparatory
efforts will have little success in halting an epidemic in fulfilling
its pandemic potentials, and crisis response is, by definition, a
reactive measure.
To successfully address the emergence of novel diseases, a new paradigm
has to be introduced into global health security, shifting our main
focus from preparedness over to prevention, and moving our intervention
further up the infection timeline. However, in order to change our
approach, we must understand the gaps that have thus far allowed EIDs to
ravage our societies.
What are we missing?
Health security measures are developed by close collaboration networks
between public health and fundamental science. With the constant
advancements in both technology and research, numerous defence
strategies have been improved. Nevertheless, the EID crisis represents a
completely novel challenge, which requires understanding the limitations
of our current approaches, particularly about the predictability and the
scope of EIDs.
Predictability
Despite the extent to which epidemics and pandemics damage a wide range
of socio-economic landscapes, there are a concerningly few initiatives
aiming to prevent large scale effects of EIDs
(18,19). This is due to
the prevailing evolutionary paradigm used in public health and research
regarding the ability of pathogens’ to colonise new hosts a.k.a. emerge
as a novel disease. The traditional scientific paradigm states that
there is strong selection acting on parasite characteristics, which
leads to extreme specialisation to a narrow range, often a single host
species. Such specialised parasites are able to better exploit host
resources, but at the same time lose their ability to infect novel host
organisms, therefore any novel colonisation must necessarily be preceded
with the right mutation appearing at the right time
(20). Due to the random and
unpredictable nature of such genetic changes, host switching events are
assumed to be rare and unpredictable
(1,21). However, this
co-evolutionary theory suffers from severe shortcomings, when compared
to empirical data: (I) its key assumption of parasites being tightly
co-adapted to a narrow range of hosts lack empirical support, (II) its
prediction regarding EIDs being rare occurrences is sharply contradicted
by the accelerating EID crisis
(22–24) and (III)
it fails to connect such novel colonizations events to environmental
changes when there is evidence that emergences cluster around climate
change perturbations
(25,26).
This contradiction between the prevailing paradigm and empirical
observations is referred to as the Parasite Paradox
(27), with a significant
consequence on how public health addresses EIDs: it deems emergence
rare, and therefore of low global health concern, and at the same time
unpredictable, thus deeming prevention efforts impossible. These wrong
predictions are the main reasons public efforts aiming to address the
EID crisis have been futile, and precisely why we need a novel
evolutionary paradigm to resolve this paradox.
The Stockholm Paradigm
The Stockholm Paradigm (SP)
(1,26,28) relies
on two Darwinian principles leading to fundamentally different
conclusions than the co-evolutionary theory.
First, evolutionary outcomes are always local. Pathogens are genetically
capable of infecting a certain range of hosts, translated as their
‘fundamental fitness space’, but only infect a subset of these that are
available to them in their environment, creating their ‘realised fitness
space’. Selection only acts on traits within the realised fitness space
and has no effect on other, potential hosts in other environments.
Pathogens with proportionally smaller realised fitness space therefore
have a higher potential of colonising a novel host, without the
necessity of evolving new capacities. This potential is referred to as
ecological fitting (29).
When viewed from a public health perspective, this means emergence is a
built in attribute of host-pathogen associations and is therefore
expected to happen frequently, especially when environmental
perturbations increase species encounters, which is what we are
witnessing with the EID crisis.
Second, evolution is conservative. In order to utilise particular
resources, pathogens will develop specialised traits. Since these traits
are phylogenetically conservative, pathogens will be able to utilise
distantly-related, naive host species upon encounter, while the same
host can serve as a resource for various pathogens
(30–32). The
recently emerged SARS-COV-2 uses the angiotensin I converting enzyme 2
(ACE2) as its main receptor, which is widely shared among distant groups
of mammals, and is the primary reason why the pathogen had established
itself in mustelids, felines and cervids, among other mammals
(33,34) Translated to a
practical view, conservative traits allow us to predict the risk an
unknown pathogen poses to human populations without having to wait for
an outbreak. Pathogenic microbes can therefore be sampled from reservoir
species and action can be taken not only to contain emergence, but to
prevent it all together.
The SP therefore changes the theoretical foundation on which our global
health security infrastructure is built. The bad news is that EIDs are
indeed frequent and should only be expected to increase in occurrence
with the intensifying globalisation and climate change. The good news,
however, is that EIDs are predictable, and preventive action can and
should be taken to avoid the next epidemic and pandemic.
Scope
When referring to EIDs, literature and policy refers to almost
exclusively human pathogens
(13,17,35).
Preparatory efforts and early action plans exclusively target human
diseases, which manifests in recommended actions for Rapid
Response and Focused Research(36,37). However, this
also narrows our view to a small subset of potentially dangerous
pathogens, while we ignore those affecting crops and livestock.
Infectious diseases decimating agricultural production are dealt with by
food security, agri-food sciences and agricultural policies, and are
barely put in the context of EIDs . Nevertheless, the loss of production
and associated costs affect regions’ economies just as much, if not more
than human diseases do. Coconut Lethal Yellowing Disease destroyed 95%
of coconut palms in a region of Mexico, killed millions of trees in
Nigeria affecting the livelihood of 30000 families, and ruined 72-99%
of trees in West Africa
(38,39). Wheat stem
rust (Puccinia graminis f. sp. ) was considered eradicated until 1998,
when a new, highly virulent strain emerged in Uganda
(40). Since then, it has
spread throughout Eastern and South Africa, the Middle East and Western
Europe, and poses a threat to over 80% of the world’s wheat varieties
(41). From those affecting
livestock, the 2014-15 avian influenza epidemic led to the culling of 45
million birds in the US, and export bans in 75 countries
(42)ongoing H5N1 avian
influenza outbreak already led to the loss of 77 million birds
(43). Within a few years,
African Swine fever (ASF) swept through Europe and Asia, destroying 20%
of Vietnam’s swine population and resulting in 141 billion USD economic
loss for China, collapsing half the world’s pork export market in a
single year (44). Apart from
the obvious socio-economic effects of food shortage and skyrocketing
food prices, policy interventions aimed at relieving damages of ASF were
suggested to have led to the emergence of COVID
(45).
Although currently considered as separate issues of human wellbeing,
food security and global health security are threatened by the same
thing: Emerging Infectious Diseases. If we understand the dynamic
allowing novel pathogens to explore and colonise new hosts, then we must
also understand that this applies to not only humans invading natural
habitats, but to our crops and livestock being placed in the close
vicinity of natural reservoirs
(46,47).
With EIDs being predictable, but much more frequent and abundant than
previously thought, health security measures have to incorporate this
new paradigm and adopt appropriate and much called for prevention
measures (48). We therefore
describe a comprehensive four-step protocol based on the SP and leading
all the way to policy implementations.
The DAMA Protocol
The DAMA - Document, Assess, Monitor, Act - is a policy plan derived
directly from the evolutionary framework of the Stockholm Paradigm,
which aims to connect evolutionary science with applied health security.
It focuses on preventing outbreaks and facilitating communication
between private and public actors, knowledge institutions and
communities directly affected (Fig 1, redrawn and modified from
(21).
Documenting pathogens has to be extended from only those
already causing diseases to those documented in wild animal and plant
populations. Taking advantage of the evolutionary context provided by
the SP, anticipatory research has to focus on potential reservoirs.
Pathogens causing disease in humans, crops or livestock are all present
in at least one other species that manifests no symptoms. Taxonomic
inventories, virological and bacteriological studies have often revealed
these pathogen-reservoir associations, which direct research focus on a
subset of species within any given area. Pathogen transmission occurs on
the interface between such reservoirs and human settlements,
agricultural areas and breeding facilities
(49–51). The
primary step in establishing a preventive protocol is collecting all
information into strategic inventories feeding into archives of host and
pathogen specimens, modes of transmission and potential vectors
(52,53). Finally,
inventories are also to include local and traditional knowledge on the
distribution, behaviour and abundance of reservoirs, which calls for the
establishment of robust science-society collaborative programs
(1,54,55).
Inventories then allow us to Assess the risk posed by
potential pathogens. A three step process first separates our potential
pathogens, from those already known and those considered to
non-pathogenic through phylogenetic triage , then usesphylogenetic assessment to determine mode of transmission,
reservoirs and potential vectors, and finally maps population genetics
and rare genotypes through population modelling .
Potential pathogens are then Monitored to create a
detailed distribution map in areas already confirmed as well as those
deemed suitable. Changes in geographic distribution, host range, mode of
transmission or disease pathology are early signs of potential emergence
on interfaces between populations of reservoirs and susceptible hosts
(47).
Adequate monitoring sets the stage for adequate Action in
policy-making. Highly dependent on the context such as legal
environment, policy modifications concern areas such as food safety,
wildlife management, veterinary medicine, public health and education.
Due to the high number of stakeholders affected by EID outbreaks,
preventive action has to be designed by multi-actor task forces
representing expertise from various sectors and scales. In practice,
this necessitates the collaborative work of scientists, private and
government practitioners, policy-makers and local experts. This
collaboration can be realised by employing transdisciplinary approaches.
The latter can be defined as “a critical and self-reflexive research
approach that relates societal with scientific problems‘ …
[and] produces new knowledge by integrating different scientific and
extra-scientific insights”
(56) and are increasingly
recognised for their potential to tackle complex real-life issues by
integrating different kinds of knowledge
(57,58).
Contrary to pandemics and large epidemics, emergence always takes place
on a small, local scale, which calls for the facilitation of bottom-up
effects and the subsequent co-accommodation of grassroots and
institutional settings. When establishing task forces putting science
into action, initiators have to consider implementation strategies on
various scales (global, regional, local) and policy environments (human,
livestock and crop health security).
Implementation strategies
on different scales
Global
Current global frameworks are all based on managing existing diseases
and increasing palliation and preparedness for those newly emerging
(59,60). Since they are
all based on the assumption that EIDs are rare and unpredictable, plans
to prevent outbreaks are slim to none. Nevertheless, most of the global
frameworks in use name prevention of disease as their main aim, which
refers to containing diseases on the level of outbreak, halting large
scale transmission and thus avoiding outbreaks from growing into
epidemics. Although we can understand restricting pathogens from
spreading beyond small, local outbreaks as preventing epidemics, we
argue that prevention should be used in the context of avoiding
emergence in the first place. This shift in epistemics is also strongly
supported by the grave predictions regarding the speed with which
smaller outbreaks can spread out in an increasingly globalised world
(17,61,62),
narrowing the time window available for containment measures.
One the one hand, global health security has to adopt a novel
evolutionary paradigm to adjust risks and predictions regarding EIDs. On
the other hand, the epistemology and definition of prevention needs to
be unified across all global guidelines to focus efforts in both
containing and preventing diseases in an evolutionary context.
Therefore, current measures have to be evaluated to determine their
applicability and limitations, and prevention has to be contextualised
within global health security.
The Prevent - Prepare - Palliate (3P) framework offers a comprehensive,
systemic characterization of existing health security initiatives and
describes how prevention can be adopted into current infrastructures
(21). Implementing
prevention into global healthcare frameworks will help identify gaps
that allow EIDs to emerge at an accelerating rate and would provide
guidelines for healthcare infrastructures to intervene on a regional
level.
Regional
Managing diseases on a regional level faces the challenge of having to
act in various different policy and cultural environments. Ranging from
upper regional levels such as international alliances (e.g. European
Union) operating within large scale legal environments such as EU
regulations through mid-regional levels concerning one or a few
neighbouring countries to lower regional levels involving small
municipalities managing local communities, regional scales are the most
diverse in terms of expertise, jurisdiction and policies. Nevertheless,
epidemics of national concern are dealt with on regional levels,
involving municipalities directly affected as well as national health
care infrastructures and public health institutions
(9). Therefore, implementing
the DAMA protocol on a regional scale requires carefully selected
methods facilitating intersectoral collaboration and defining outcomes
accommodating local policy environments.
Living Labs
From the toolkits of transdisciplinary methods, Living Labs (LLs)
provide an opportunity to establish solid, well thought out task forces
bringing the skills and capacities of different actors required for
addressing a particular issue together
(63). Living Labs can be
defined as both “an arena (i.e., geographically or institutionally
bounded spaces) and … an approach for intentional collaborative
experimentation of researchers, citizens, companies and local
governments” (64). It makes
them suitable for dealing with healthcare issues, as they are designed
to foster intersectoral communication and collaboration, and thus
increase the feasibility of intervention plans by fitting them to local
policy environments and interests of affected stakeholders
(65). If designed and
implemented well, the LL approach can also help avoid stumbling blocks
(e.g. disciplinary boundaries and silos between science, practice and
society, low feasibility in diverse policy environments, low level of
adaptability to local cultural, societal, environmental settings,
decreasing trust in policy and politics, etc.) by involving diverse
experts on legal limitations, local settings and market conditions, and
finally foster knowledge exchange and widen professional networks.
Containing outbreaks or epidemics requires a joint collaboration between
private and public sectors, as well as science and society, and
prevention is no different. Current solutions are mostly characterised
by hasty and temporary collaborations formed under the pressure of a
health emergency. Living Labs are potentially a very impactful approach
for dealing with EID crises. They have been proliferating in Europe
since 2006, when the European Network of Living Labs (ENoLL) was founded
as a platform for best practice exchange, and have since been
successfully adopted in domains such as food bioeconomy, agriculture,
environmental, urban and rural development
(64,66,67).
However, to date Living Labs have hardly ever been applied to the area
of EIDs. Apart from the benefits of the LL approach discussed above more
generally, LLs can also enable and foster discussion between
authorities, science and the public thereby addressing the dire
consequences of public distrust in science and science-based policies
revealed by the COVID-19 pandemic has revealed the dire consequences of
public distrust in science and science-based policies
(68,69).
Given the various actors impacted by infectious disease outbreaks, LL
setups are able to generate solutions across disciplines, making them a
‘proliferating approach to working in a transdisciplinary fashion’
(57). Stakeholders are
selected based on their expertise and involvement in the context of
EIDs, making them highly adaptable and specific to the issue
investigated. Selection must also consider the highest-level
decision-makers needed for efficient intervention (municipality
governance and policy-makers, national government officials, regional
public health authorities, etc.) Participants generally represent four
larger sectors (Figure 1.).
- Public actors - policy- and decision-makers, legal experts
and government officials; expertise in the legal environment and
regulatory role in the long-term management of the outcome. Typical
actors for disease management are Public Health Authorities,
Municipality Governance or Food Safety Control.
- Private actors - private institutions, organisations and
companies affected by the emergence; insights into practical and
industrial implementability of intervention plans. Managing disease
will be of interest to agricultural organisations and farmers’
associations, livestock breeders and food production companies, travel
agencies or pharmaceutical companies.
- Knowledge institutions - scientific expertise on the emerging
pathogen generate predictions related to transmission, epidemic and
pandemic potential and risk assessment. Partners to consider in
relation to EID are university research groups, independent research
institutions and scientific organisations (e.g. Chatham House, Milken
Institute).
- Local citizens - it is crucial to include members of the
community directly affected by potential emergence. In addition to
increasing feasibility of the intervention plans among local
conditions, involvement raises awareness of healthcare threats and
provides the community with a sense of ownership over the situation.
An emphasis must be placed on reaching out to local Citizen Science
Programs who have extensive experience in not only local settings, but
research processes.